Brief Summary
Phase I/II study: Phase 1 is an open-label, safety study, patients who previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1\*10\^6 cells) HS-410 monotherapy. Phase 2, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1\*10\^6 cells) or high dose (1\*10\^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. Patients who do not receive BCG will be enrolled into an open-label, non-randomized group receiving high dose (1\*10\^7 cells) intradermal HS-410 monotherapy.
Brief Title
A Phase 1/2 Study of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer After TURBT
Detailed Description
This study is a two part study: Phase I and Phase II. The Phase 1 portion is an open-label, safety study. Patients will have previously received 3-6 instillations of weekly intravesical Bacillus Calmette-Guerin (BCG) induction therapy (as standard of care) followed by low dose intradermal (1\*10\^6 cells) HS-410 monotherapy. In Phase 2, patients will be assigned to treatment groups based on whether they will receive induction BCG in the typical post-TURBT window. If the investigator plans to administer BCG, patients will be randomized to one of three blinded (physician-patient), placebo-controlled groups and receive either intradermal placebo or low dose (1\*10\^6 cells) or high dose (1\*10\^7 cells) vesigenurtacel-L in combination with induction and maintenance intravesical BCG. If patients will not receive BCG, they will be enrolled into an open-label, non-randomized group and receive high dose (1\*10\^7 cells) intradermal HS-410 monotherapy.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Bladder Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed non-muscle invasive bladder cancer \[Ta, T1 or Tis (CIS)\] that has been removed by transurethral resection
* Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size \> 3cm, early recurrence (\<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
* Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment \> 12 months prior to the baseline staging procedure.
* Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
* Adequate laboratory parameters
Exclusion Criteria:
* Human immunodeficiency virus (HIV) infection or immunodeficiency disorders, either primary or acquired
* Infections or intercurrent illness requiring active therapy
* Any condition requiring active steroid or other immunosuppressive therapy
* Active malignancies within the past 12 months except negligible risk of metastasis or death treated with expected curative outcome.
* Prostate pelvic radiation within the past 12 months
* Significant cardiac impairment
* Current alcohol or chemical abuse, or mental or psychiatric condition precluding protocol compliance
* Pregnant or nursing
* Allergy to soy, egg, or peanut products
* Receiving another investigational agent (30 day wash-out required prior to first dose)
* Neo-adjuvant therapy prior to baseline staging procedures for the current occurrence of non-muscle invasive bladder cancer
* Prior treatment with a cancer vaccine for this indication
* Prior vaccination with BCG for tuberculosis disease
* Prior splenectomy
* Histologically or cytologically confirmed non-muscle invasive bladder cancer \[Ta, T1 or Tis (CIS)\] that has been removed by transurethral resection
* Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size \> 3cm, early recurrence (\<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
* Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment \> 12 months prior to the baseline staging procedure.
* Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
* Adequate laboratory parameters
Exclusion Criteria:
* Human immunodeficiency virus (HIV) infection or immunodeficiency disorders, either primary or acquired
* Infections or intercurrent illness requiring active therapy
* Any condition requiring active steroid or other immunosuppressive therapy
* Active malignancies within the past 12 months except negligible risk of metastasis or death treated with expected curative outcome.
* Prostate pelvic radiation within the past 12 months
* Significant cardiac impairment
* Current alcohol or chemical abuse, or mental or psychiatric condition precluding protocol compliance
* Pregnant or nursing
* Allergy to soy, egg, or peanut products
* Receiving another investigational agent (30 day wash-out required prior to first dose)
* Neo-adjuvant therapy prior to baseline staging procedures for the current occurrence of non-muscle invasive bladder cancer
* Prior treatment with a cancer vaccine for this indication
* Prior vaccination with BCG for tuberculosis disease
* Prior splenectomy
Inclusion Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed non-muscle invasive bladder cancer \[Ta, T1 or Tis (CIS)\] that has been removed by transurethral resection
* Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size \> 3cm, early recurrence (\<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
* Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment \> 12 months prior to the baseline staging procedure.
* Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
* Adequate laboratory parameters
* Histologically or cytologically confirmed non-muscle invasive bladder cancer \[Ta, T1 or Tis (CIS)\] that has been removed by transurethral resection
* Either: (i) high-risk disease, defined as T1 and/or high-grade and/or CIS or (ii) intermediate-risk disease, defined as Ta low-grade with at least 3 of the following 4 risk factors: multiple tumors, tumor size \> 3cm, early recurrence (\<1 year from previous staging procedure), or recurrence with a frequency of more than once in any 12 month period
* Not have received bacillus Calmette-Guérin (BCG) or have completed previous BCG treatment \> 12 months prior to the baseline staging procedure.
* Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
* Adequate laboratory parameters
Gender
All
Gender Based
false
Keywords
TURBT
Bladder
Cancer
GP96
Vaccine
Immunotherapy
Heat Biologics
BCG
Bacillus Calmette-Guerin
Bacillus Calmette-Guérin
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02010203
Org Class
Industry
Org Full Name
Heat Biologics
Org Study Id
HS410-101
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase 1/2, Placebo-Controlled, Randomized Study to Evaluate the Safety, Immune Response & Clinical Activity of HS-410 in Patients With Non-Muscle Invasive Bladder Cancer Who Have Undergone Transurethral Resection of Bladder Tumor (TURBT)
Primary Outcomes
Outcome Description
To evaluate the safety and tolerability of vesigenurtacel-L
Outcome Measure
Phase 1: Safety and Tolerability
Outcome Time Frame
Up to 3 years.
Outcome Description
Arm 1, 2, 3: 1-year DFS in patients with NMIBC treated with BCG in combination with blinded study product (one of two doses of vesigenurtacel-L or placebo) Arm 4: 1-year DFS in patients with NMIBC treat1fv 9 with high dose vesigenurtacel-L monotherapy
One-year disease-free survival will be defined as the proportion of patients who are free from recurrent disease, progressive disease, and alive one year after the date of randomization/treatment assignment
One-year disease-free survival will be defined as the proportion of patients who are free from recurrent disease, progressive disease, and alive one year after the date of randomization/treatment assignment
Outcome Measure
Phase 2: 1-year Disease-Free Survival
Outcome Time Frame
One year
Secondary Outcomes
Outcome Description
Evaluate the proportion of patients with recurrence at 3, 6, 12, 18, and 24 months
Outcome Time Frame
Up to 2 years
Outcome Measure
Proportion of Patients With Recurrence at 3, 6, 12, 18, and 24 Months
Outcome Description
Evaluate the proportion of patients with progressive disease at 3, 6, 12, 18, and 24
Outcome Time Frame
Up to 2 years
Outcome Measure
Proportion of Patients With Progressive Disease at 3, 6, 12, 18, and 24 Months
Outcome Description
Evaluate Disease Free Survival at 3, 6, 18 and 24 months
Outcome Time Frame
Up to 2 years
Outcome Measure
Disease-free Survival at 3, 6, 18, and 24 Months
Outcome Description
Evaluate overall Disease Free Survival
Outcome Time Frame
Up to 3 years
Outcome Measure
Overall Disease-free Survival
Outcome Description
Evaluate overall survival (OS)
Outcome Time Frame
Up to 3 years
Outcome Measure
Overall Survival, Expressed as the Number of Participants Alive
Outcome Time Frame
Up to 2 years
Outcome Measure
Proportion of Patients Undergoing Repeat Transurethral Resection of Bladder Tumor (TURBT) by 12 and 24 Months
Outcome Description
Evaluate the proportion of patients undergoing cystectomy by 12 and 24 months from randomization
Outcome Time Frame
Up to 2 years
Outcome Measure
Proportion of Patients Undergoing Cystectomy by 12 and 24 Months
Outcome Description
Evaluate the proportion of patients with immunologic response of peripheral blood mononuclear cells (PBMCs) via intracellular cytokine staining (ICS) by flow cytometry and/or ELISPOT on CD8+ cells following vesigenurtacel-L vaccination
Outcome Time Frame
Up to 2 years
Outcome Measure
Immunologic Response of PBMCs Via Intracellular Cytokine Staining (ICS) by Flow Cytometry and/or Enzyme-linked Immunosorbent Spot (ELISPOT) on CD8+ Cells After HS-410 Vaccination as Compared to Baseline.
Outcome Description
Evaluate immunologic response of PBMCs (analysis of surface markers, CD3, CD4, CD8, CD19, CD25, CD45, CD56, FoxP3, and degranulation) and stimulation analysis via ICS of interferon gamma (IFNγ) and granzyme B (gzB)
Outcome Time Frame
Up to 3 years
Outcome Measure
Immunologic Response of Peripheral Blood Mononuclear Cells (PBMCs) and Stimulation Analysis Via ICS in Baseline and Post-treatment Biopsies, if Clinically Indicated
Outcome Description
Evaluate total PBMC counts by flow cytometry, including lymphocyte subsets (B cells, helper T-cells, cytotoxic T-cells, natural killer (NK) cells and T-reg)
Outcome Time Frame
Up to 3 years
Outcome Measure
Total PBMC Counts by Flow Cytometry
Outcome Description
Evaluation of pre-treatment tumor tissue for antigen expression
Outcome Time Frame
At screening
Outcome Measure
Tumor Antigen Expression
Outcome Description
Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs
Outcome Time Frame
Up to 3 years
Outcome Measure
Tumor Infiltrating Lymphocytes (TILs)
Outcome Description
Evaluation of tumor tissue obtained from repeat biopsy, if clinically indicated, for presence of TILs, T cell receptor sequencing of peripheral blood T cells before and during the course of treatment.
Outcome Time Frame
Up to 2 years
Outcome Measure
T Cell Receptor Sequencing of Peripheral Blood T Cells Before and During Treatment
Outcome Description
Phase 2 only Evaluate the safety of the combination of vesigenurtacel-L and BCG
Outcome Time Frame
Up to 1 year
Outcome Measure
Safety of the Combination of the HS-410 and BCG
Outcome Description
Phase 2 only Evaluate the safety of high dose vesigenurtacel-L monotherapy
Outcome Time Frame
Up to 3 years.
Outcome Measure
Safety of the High Dose HS-410 Monotherapy
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Alexander Sankin
Investigator Email
asankin@montefiore.org
Investigator Phone